Invasive fungal infections caused by species of Candida, Cryptococcus, and Aspergillus afflict more than 1.5 million humans globally each year with a staggering mortality rate that often exceeds 50%.1 Candida is the most frequent source of fungal infections worldwide; notably, Candida albicans is the fourth-leading cause of bloodstream infections, and is particularly problematic in immunocompromised patients.2 There has been a global increase in the prevalence of invasive Candida infections in part due to the emergence of non-albicans Candida species including Candida glabrata, Candida tropicalis, Candida parapsilosis, and Candida krusei.3, 4 In addition to Candida, species of Cryptococcus (including C. neoformans and C. gatti) are responsible for more than one million new invasive fungal infections each year that result in an astounding 625,000 deaths.5 Patients co-infected with HIV are susceptible to severe cryptococcal infections that manifest primarily as pneumonia or meningoencephalitis.6 The third fungal pathogen of concern involves species of Aspergillus (namely A. fumigatus) which are responsible for more than 300,000 fungal infections each year.7 Invasive disease (particularly pulmonary infections) caused by Aspergillus primarily occur in patients with underlying conditions such as AIDS, cancer, cystic fibrosis, asthma, or individuals undergoing solid organ transplants. The severity of such infections can be seen by the low rate of survival (59%) reported for solid organ transplant recipients afflicted with invasive aspergillosis.8 
The difficulty in treating invasive fungal infections has been exacerbated by the limited number of approved antifungal drugs. Currently, only three structurally-distinct classes of antifungal drugs are primarily used for treatment of invasive fungal infections—azoles (such as fluconazole), polyenes (such as amphotericin B), and echinocandins (such as caspofungin).9 All three classes exert their antifungal activity by interfering with synthesis of a key component of the fungal cell membrane (ergosterol synthesis by both azoles and polyenes) or cell wall (β(1,3)-d-glucan synthesis by echinocandins).9 Azole antifungals, including fluconazole, are considered the drugs of choice given their high oral bioavailability and reduced toxicity to host tissues. However, the clinical utility of fluconazole and other antifungal drugs has become increasingly limited due to the emergence of clinical isolates exhibiting resistance to these agents.10, 11 This necessitates the development of new therapeutic agents. However, only one new antifungal drug class has been successfully developed in the past 30 years.12 The development of new antifungal agents is very challenging given fungi and mammals are both eukaryotes; thus many proteins that are potential targets for antifungal therapy are also found in human cells, opening the door for potential toxicity concerns.12, 13 There remains a need to identify antifungal compounds that are not toxic to human cells.